Controlled release dosage drug forms represent a form of drug administration, which has been largely adapted to the therapeutic requirements and the drug, the release of which is controlled by mechanisms which are not affected or affected to only an insignificant extent by physiological conditions such as pH, enzymes, nature and quality of the food. Depending on the control principles employed, diffusion-, matrix-, swelling-membrane-, or chemically-controlled release can occur. According to the more comprehensive definition of the American Food and Drug Administration, controlled-release products are formulations intended to release the active component at rates which differ significantly from the immediate release from corresponding compositions not having any delaying properties. This definition includes all types of retard (sustained-release) drug forms, as well as those with fixed time release properties, such as preparations resistant to gastric juices.
A number of methods for preparing such formulations are known from the literature. For example, the European patent No. 324,989 discloses the preparation of a new pharmaceutical formulation with controlled release by means of wet granulation, the active ingredient being mixed with appropriate inactive ingredients and granulated in 95% ethanol. After subsequent drying, the granulate obtained is screened to the desired size.
Formulations with a controlled release can also be prepared by melt granulation, as described, for example, in the German patent No.2,426,812. The binder component is present here in a liquid aggregate state, since the process temperature for the granulation is higher than the melting temperature of the low-melting component.
Further methods of producing formulations with controlled release, known from the art, are various granulation and extrusion methods as described, for example, in German patent No. 4,408,326.
The active compositions, obtained with the known methods, in some cases have an incomplete release delay or much scatter in the individual values for the release of active ingredient. This can have a particularly disadvantageous effect for patients, since it cannot be assured that the desired plasma concentration and the corresponding level of bioavailability can be maintained.